Objective: Novel, highly effective disease-modifying therapies have revolutionized multiple sclerosis (MS) care. However, evidence from large comparative studies on important safety outcomes, such as cancer, is still lacking.
Methods: In this nationwide register-based cohort study, we linked data from the Swedish MS register to the Swedish Cancer Register and other national healthcare and census registers. We included 4187 first-ever initiations of rituximab, 1620 of fingolimod, and 1670 of natalizumab, in 6136 MS patients, age-sex-and-location matched to 37801 non-MS general population subjects. Primary outcome was time to first invasive cancer.
Results: We identified 78 invasive cancers among treated patients: rituximab 33 (incidence rate, IR, per 10,000 person years 34.4 [95% confidence interval 23.7-48.3]), fingolimod 28 (44.0 [29.2-63.5]), and natalizumab 17 (26.0 [15.1-41.6]). The general population IR was 31.0 [27.8-34.4]. Adjusting for baseline characteristics, we found no difference in risk of invasive cancer between rituximab, natalizumab, and the general population, but a possibly higher risk with fingolimod compared to the general population (1.53 [0.98-2.38]) and rituximab (hazard ratio 1.68 [1.00-2.84]). Interpretation In this first, large, comparative study of three highly effective MS disease-modifying therapies, no increased risk of invasive cancer was seen with rituximab and natalizumab, compared to the general population. However, there was a borderline-significant increased risk with fingolimod, compared to both the general population and rituximab. It was not possible to attribute this increased risk to any specific type of cancer and further studies are warranted to validate these findings.